- Product Name:
- RIFAMPIN ''LEPETIT''
- Product Categories:
- Peptide Synthesis/Antibiotics
- Antibiotics for Research and Experimental Use
- Others (Antibiotics for Research and Experimental Use)
- Antibiotic Explorer
- Intermediates & Fine Chemicals
- Isotope Labeled Compounds
- Chiral Reagents
- Isotope Labelled Compounds
- Mol File:
Rifampicin Chemical Properties
- Melting point:
- 183°C (dec.)
- Boiling point:
- 761.02°C (rough estimate)
- 1.1782 (rough estimate)
- refractive index
- 1.6000 (estimate)
- storage temp.
- chloroform: soluble50mg/mL, clear
- 1.7, 7.9(at 25℃)
- faint red to very dark red
- Water Solubility
- Soluble in DMSO or methanolSoluble in water, ethyl acetate, chloroform, methanol, tetrahydrofuran and dimethyl sulfoxide.
- 3 (Vol. 24, Sup 7) 1987
- EPA Substance Registry System
- Rifampin (13292-46-1)
- Language:English Provider:3-[[(4-methyl-1-piperazinyl)imino]methyl]-rifamycin
- Language:English Provider:SigmaAldrich
Rifampicin Usage And Synthesis
Inhibitor of Nucleic Acid Synthesis
Rifampicin and other compounds of the ansamycin group specifically inhibit DNA-dependent RNA polymerase; that is, they prevent the transcription of RNA species from the DNA template. Rifampicin is an extremely efficient inhibitor of the bacterial enzyme, but fortunately eukaryotic RNA polymerase is not affected. RNA polymerase consists of a core enzyme made up of four polypeptide subunits, and rifampicin specifically binds to the β subunit where it blocks initiation of RNA synthesis, but is without effect on RNA polymerase elongation complexes. The structural mechanism for inhibition of bacterial RNA polymerase by rifampicin has recently been elucidated. The antibiotic binds to the β subunit in a pocket which directly blocks the path of the elongating RNA chain when it is two to three nucleotides in length. During initiation the transcription complex is particularly unstable and the binding of rifampicin promotes dissociation of short unstable RNA DNA hybrids from the enzyme complex. The binding pocket for rifampicin, which is absent in mammalian RNA polymerases, is some 12 Å away from the active site.
Red to Orange Crystalline Solid
Semisynthetic antibiotic. Antibacerial (tuberculostatic)
ChEBI: A member of the class of rifamycins that is a a semisynthetic antibiotic derived from Amycolatopsis rifamycinica (previously known as Amycolatopsis mediterranei and Streptomyces mediterranei)
Rifampin (300 to 450 mg daily) is very effective in relieving the pruritus of primary biliary cirrhosis, by inhibiting hepatic bile uptake and stimulating mixed-function oxidases. Liver enzymes should be monitored to detect druginduced hepatitis.
Rifadin (Sanofi Aventis); Rimactane (Actavis).
It exhibits potent activity in vitro against Gram-positive cocci, including methicillin-resistant staphylococci (MIC <0.025–0.5 mg/L) and penicillinresistant pneumococci. Enterococci are less susceptible. Gram-positive bacilli, including Bacillus spp., Clostridium difficile, Corynebacterium spp. and Listeria monocytogenes, are highly susceptible (MIC 0.025–0.5 mg/L). The pathogenic Neisseria and Moraxella spp. are also highly susceptible.
Enteric Gram-negative bacteria are generally less sensitive (MIC 1–32 mg/L), but Bacteroides fragilis is highly susceptible. Among other Gram-negative bacilli, Haemophilus influenzae, H. ducreyi, Flavobacterium meningosepticum and Legionella spp. are highly susceptible (MIC <0.025–2 mg/L). Chlamydia trachomatis and Chlamydophila psittaci are inhibited by low concentrations (0.025–0.5 mg/L).
Most strains of M. tuberculosis, M. kansasii and M. marinum are inhibited by <0.01–0.1 mg/L, but M. fortuitum and members of the M. avium complex are resistant. M. leprae is highly sensitive.
Rifampicin is active against some eukaryotic parasites through inhibition of the prokaryote-like polymerase of kinetoplasts or mitochondria. Maturation of Plasmodium falciparum is inhibited by 2–10 mg/L; at higher concentrations Leishmania spp. are also inhibited.
High concentrations inhibit growth of a variety of poxviruses by interference with viral particle maturation; viral reverse transcriptase is unaffected.
Most large bacterial populations contain resistant mutants, which readily emerge in the presence of the drug and can emerge during treatment. The mutation rate to resistance in Staph. aureus, Str. pyogenes, Str. pneumoniae, Esch. coli and Proteus mirabilis is about 10–7 and that to M. tuberculosis and M. marinum 10–9–10–10. Primary resistance in M. tuberculosis remained low for many years, but is increasing.
Resistance is of the one-step type, and several classes of mutants exhibiting different degrees of resistance can be selected by exposing a large population to a relatively low concentration of the drug. Some of these mutants may be susceptible to other rifamycin derivatives.
Resistance is due to a change in a single amino acid of the β subunit of DNA-dependent RNA polymerase, which no longer forms a stable complex with rifampicin. It is not transferable and there is no cross-resistance with any other antibiotic class. The susceptible strains of the gastrointestinal flora become rapidly resistant during rifampicin treatment without alteration in the flora composition, and revert to susceptibility within a few weeks of cessation of treatment.
Rifampin (USAN). Molecular weight: 822.95.
A semisynthetic derivative of rifamycin SV, available for oral administration or intravenous infusion and in several combined formulations with other antimycobacterial drugs. It is poorly soluble in water, but soluble in organic solvents.
Mechanism of action
Rifampin is a semisynthetic macrocyclic antibiotic produced from Streptomyces mediterranei. It is a large lipidsoluble molecule that is bactericidal for both intracellular and extracellular microorganisms. Rifampin binds strongly to the β-subunit of bacterial DNA-dependent RNA polymerase and thereby inhibits RNA synthesis. Rifampin does not affect mammalian polymerases.
Rifampin is well absorbed orally, and a peak serum concentration is usually seen within 2 to 4 hours. Drug absorption is impaired if rifampin is given concurrently with aminosalicylic acid or is taken immediately after a meal. It is widely distributed throughout the body, and therapeutic levels are achieved in all body fluids, including cerebrospinal fluid. Rifampin is capable of inducing its own metabolism, so its half-life can be reduced to 2 hours within a week of continued therapy. The deacetylated form of rifampin is active and undergoes biliary excretion and enterohepatic recirculation. Most of the drug is excreted into the GI tract and a small amount in the urine.Moderate dose adjustment is required in patients with underlying liver disease.
Cmax300 mg oral ：4 mg/L after 2 h
600 mg oral：10 mg/L after 2 h
Plasma half-life：2.5 h
Volume of distribution：1.5 L/kg
Plasma protein binding：80%
Rifampicin is virtually completely absorbed when administered orally, but substantial differences in blood levels have been reported in comparisons of capsules or tablets from different manufacturers. Peak plasma levels differ noticeably between individuals. Food affects absorption, the peak plasma levels being delayed and about 2 mg/L lower after a meal. Although the AUC and the length of time for which effective antibacterial levels are maintained are little affected, it is preferable that patients take the drug before meals.
Intravenous administration produces AUCs and elimination half-lives similar to those obtained after oral doses.
The lipid solubility of the drug facilitates its distribution. It is widely distributed in the internal organs, bones and fluids, including tears, saliva, ascitic fluid and abscesses. It penetrates into cells and is active against intracellular bacteria. Low concentrations are found in the cerebrospinal fluid (CSF), but these are substantially higher when the meninges are inflamed. Concentrations around 60% of the simultaneous plasma value were found in the heart valves of patients receiving a 600 mg dose before surgery.
Rifampicin is metabolized principally to its desacetyl derivative, which is also antimicrobially active, and this process is accelerated by its stimulatory effect on hepatic microsomal enzymes. As a consequence, hepatic clearance increases on continuous administration and, especially with high doses, the serum half-life becomes shorter after a few days of treatment.
The main route of elimination is secretion into the bile, a process that is dose dependent, being efficient at low dosage but limited at high dosage. As a result, the dose determines the proportion excreted via the bile or passing the liver to be excreted in the urine. Because there is a limit to the rate at which the liver can deliver the drug to the bile, the elimination half-life after a 600 mg dose rises to 3 h and may be as long as 5 h with a 900 mg dose.
The desacetyl compound is mainly found in the bile, where the parent compound accounts for only 15% of the total. Plasma levels are increased by hepatic insufficiency and biliary obstruction, and by probenecid, which depresses hepatic uptake. The drug escaping biliary excretion appears in the urine, to which it imparts an orange–red color, the parent compound and the desacetyl metabolites being present in about equal proportions. The plasma concentration and half-life are not significantly affected by renal failure. The drug is not removed by hemodialysis.
The incidence of hepatotoxicity was significantly higher when rifampin was combined with isoniazid than when either agent was combined with ethambutol. Allergic and sensitivity reactions to rifampin have been reported, but they are infrequent and usually not serious. Rifampin is a powerful inducer of hepatic cytochrome P450 oxygenases. It can markedly potentiate the actions of drugs that are inactivated by these enzymes. Examples include oral anticoagulants, barbiturates, benzodiazepines, oral hypoglycemic agents, phenytoin, and theophylline. Rifampin is also used to eradicate the carrier state in asymptomatic carriers of Neisseria meningitidis to prevent outbreaks of meningitis in high-risk areas such as military facilities. Serotyping and sensitivity tests should be performed before its use because resistance develops rapidly. However, a daily dose of 600 mg of rifampin for 4 days suffices to eradicate sensitive strains of N. meningitidis. Rifampin has also been very effective against M. leprae in experimental animals and in humans. When it is used in the treatment of leprosy, rifampin should be combined with dapsone or some other leprostatic agent to minimize the emergence of resistant strains of M. leprae. Other, nonlabeled uses of rifampin include the treatment of serious infections such as endocarditis and osteomyelitis caused by methicillin-resistant S. aureus or S. epidermidis, Legionnaires disease when resistant to erythromycin, and prophylaxis of H. influenzae induced meningitis. Rifampin occurs as an orange to reddish brown crystalline powder that is soluble in alcohol but only sparingly soluble in water. It is unstable to moisture, and a desiccant (silica gel) should be included with rifampin capsule containers. The expiration date for capsules stored in this way is 2 years.
Tuberculosis (in combination with other antituberculosis agents; see Ch. 58)
Leprosy (in combination with other antileprotic agents; see Ch. 57)
Serious infection with multiresistant staphylococci and pneumococci (in combination with a glycopeptide)
Elimination of nasopharyngeal carriage of Neisseria meningitidis and H. influenzae.
Rifampin is a first-line antitubercular drug used in the treatment of all forms of pulmonary and extrapulmonary tuberculosis. Rifampin is an alternative to isoniazid in the treatment of latent tuberculosis infection. Rifampin also may be combined with an antileprosy agent for the treatment of leprosy and to protect those in close contact with patients having H. influenza type b and N. meningitidis infection; rifampin is also used in methicillin-resistant staphylococcal infections, such as osteomyelitis and prosthetic valve endocarditis.
The most commonly observed side effects are GI disturbances
and nervous system symptoms, such as nausea,
vomiting, headache, dizziness, and fatigue.Hepatitis
is a major adverse effect, and the risk is highest in patients
with underlying liver diseases and in slow isoniazid
acetylators; the rate of hepatotoxicity is increased
if isoniazid and rifampin are combined.
Other major untoward reactions are the result of rifampin’s ability to induce hepatic cytochrome P-450 enzymes, leading to an increased metabolism of many drugs; this action has especially complicated the treatment of tuberculosis in HIV-infected patients whose regimen includes protease inhibitors and nonnucleoside reverse transcriptase. Since rifabutin has relatively little of these effects, it is commonly substituted for rifampin in the treatment of tuberculosis in HIV-infected patients.
Hypersensitivity reactions, such as pruritus, cutaneous vasculitis, and thrombocytopenia, are seen in some patients, and an immune-mediated systemic flulike syndrome with thrombocytopenia also has been described. Rifampin imparts a harmless red-orange color to urine, feces, saliva, sweat, tears, and contact lenses. Patients should be advised of such discoloration of body fluids.
Rifampicin is relatively non-toxic, even when administered for a long period (as in the treatment of tuberculosis). However, several unwanted effects, including pink staining of soft contact lenses, are associated with its use. Other reactions can be divided into those associated with daily or intermittent administration, and those found only with intermittent therapy.
Suspected carcinogen with experimental neoplastigenic and teratogenic data. Poison by intraperitoneal and intravenous routes. Moderately toxic to humans by ingestion. Moderately experimentally toxic by ingestion and subcutaneous routes. Human systemic effects by ingestion: conjunctiva irritation, iritis (inflammation of the iris), other eye effects, dermatitis. Experimental reproductive effects. Human mutation data reported. When heated to decomposition it emits toxic fumes of NOx.
This macrolide antibiotic crystallises form Me2CO in red-orange plates. It has UV max at 237, 255, 334, and 475nm ( 33,200, 32,100, 27,000 and 15,400) at pH 7.38. It is stable in Me2SO and H2O and is freely soluble in most organic solvents but slightly soluble in H2O at pH <6. [Binda et al. Arzneim.-Forsch 21 1907 1971.] It inhibits cellular RNA synthesis without affecting DNA [Calvori et al. Nature 207 417 1965].
- 010-82848833- ;010-82848833-
- RIFAMPIN, [4-METHYLPIPERAZINE-3H]-
- RIFAMYCIN SV-3 FORMYL
- RIFAMYCIN SODIUM
- R 761
- N-Demethyl Rifampin
- Rifamycin, 4-O-(carboxymethyl)-
- Methyl acetate
- RIFAMYCIN SV
- Methyl salicylate
- Rifamycin Sodium
- Methyl bromide
- METSULFURON METHYL